US4506079A - Process for preparing indoles - Google Patents

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US4506079A
US4506079A US06/127,521 US12752180A US4506079A US 4506079 A US4506079 A US 4506079A US 12752180 A US12752180 A US 12752180A US 4506079 A US4506079 A US 4506079A
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aromatization
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halogen
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Makiko Sakai
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Shionogi and Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/10—Spiro-condensed systems

Definitions

  • This invention relates to novel 1,4-dioxaspiro[4,5]decene compounds of the following formula (I) useful as intermediates for producing 3-substituted-2-hydroxypropyl aryl ethers, the latter compounds being clinical ⁇ -blockers: ##STR2## (wherein X is a hydrogen or halogen;
  • one of P and R combined together with Q represents lower alkylene or alkenylene optionally interrupted by O, N or S and optionally substituted by lower alkyl, lower aralkyl, lower carboxylic acyl, or carboxy or protected carboxy, hydroxy, lower alkoxy, lower acyloxy, oxo, amino, lower alkylamino, lower acylamino, nitro, nitroso, lower alkylthio, lower sulfonic acyl or halogen; the remaining R or P is hydrogen or halogen;
  • Y is halogen, hydroxy, lower acyloxy, amino, lower alkylamino, lower aralkylamino, lower acylamino, di-lower alkylamino, lower alkyleneamino, N-lower alkyl-N-lower aralkylamino, di-lower acylamino, N-lower alkyl-N-lower acylamino or N-tri-lower alkylsilylamino;
  • ⁇ -blockers are being evaluated as being useful vasodilators as well as hypotensives.
  • a convenient and economic route for producing these ⁇ -blockers is provided starting from less expensive starting materials according to the following reaction scheme. Namely, a cyclohexenone compound (II) or its reactive derivative is condensed with a 3-substituted propyleneglycol compound (III) or its reactive derivative in the presence of an acid catalyst (IV) to give a 2-(substituted methyl)-1,4-dioxaspiro[4,5]decene compound (I), which in turn is subjected to aromatization to give an objective 3-substituted-2-hydroxypropyl aryl ether (V): ##STR3## (wherein P, Q, R, X, Y and the dotted line are as defined above)
  • aryl part preferably means C 6 to C 10 and for others means C 1 to C 10 ;
  • halogen means chlorine, bromine or iodine; and
  • acyl may be an acyl group of a carboxylic, sulfonic, sulfenic, phosphoric or carbonic acid.
  • novel 2-(substituted methyl)-1,4-dioxaspiro[4,5]decene compounds (I) are represented by the following formula: ##STR4## (in which P, Q, R, X, Y and the dotted line are as defined above).
  • representative lower alkylene as the divalent group bridging Q and P or R includes trimethylene, tetramethylene, pentamethylene, propylene and cyclohexan-1,4-diyl.
  • Representative lower alkenylene as the divalent group bridging Q and P or R may be 1-propene-1,3-diyl, 1-butene-1,4-diyl, 1-pentene-1,3-diyl or 1,3-butadiene-1,4-diyl.
  • alkylene or alkenylene interrupted by a hetero atom selected from O, N and S in its chain include the divalent groups of the following formula: ##STR5##
  • novel 2-substituted methyl-1,4-dioxaspiro[4,5]decene compounds (I) of this invention can be prepared by condensing a cyclohexenone compound (II) or its reactive derivative with a 3-substituted propyleneglycol compound (III) or its reactive derivative in the presence of an acid catalyst (IV) for dehydrating condensation according to the following reaction scheme: ##STR16## or reactive derivative (wherein P, Q, R, X, Y and the dotted line are as defined above)
  • Said cyclohexenone compound (II) is a substance known or easily producible by a conventional method from easily available substances. Its reactive derivative can be in ketal, hemiketal, enol ether, acyl hemiacetal, diacyl ketal, enol ester, enamine or like form.
  • Said 3-substituted propyleneglycol compound (III) is a substance known or easily producible by a known method from easily available substances.
  • Its reactive derivative can be an anhydro derivative (i.e. epoxide), N,N-di-lower alkyl-lower alkanamide acetal, glycol sulfite, O,O-di-lower alkylenedioxysilicone derivative, O,O-lower alkylidene derivative or like reactive form.
  • Said acid catalyst (IV) can be a mineral acid, lower hydrocarbonsulfonic acid, strong lower carboxylic acid e.g. halogenoacetic acid or Lewis acid. Specific examples of these include hydrochloric acid, sulfuric acid, phosphoric acid, acid ion-exchange resins, oxalic acid, trifluoroacetic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, ammonium chloride, calcium chloride, ferric chloride, calcium acetylide, stannic chloride, zinc chloride, boron trichloride, magnesium chloride, aluminum chloride and the like.
  • This reaction is carried out in an inert solvent.
  • the reaction can be accelerated by removing water formed during the reaction when free glycol (III) is used as the reagent.
  • Preferable solvents are those which can dissolve the cyclohexenone compound (II) or its reactive derivative and 3-substituted-propyleneglycol compound (III) or its reactive derivative used. More preferable solvents include conventional hydrocarbon-, halogenohydrocarbon-, ether-, ester-, N,N-di-lower alkyl-lower alkanamide-, nitrile-, sulfoxide-, carboxylic acid-, alcohol- and like solvents and a mixture of two or more of these.
  • compounds (II) or (III) can be used as the solvent.
  • azeotropic dehydration using e.g. Dean-Stark trap can preferably be applied.
  • Addition of an inert drying material e.g. Molecular Sieves, into the reaction medium is also a preferable choice.
  • the reaction can be carried out at a temperature range of from minus 50° C. to 150° C. for up to several days.
  • reaction of this step is a ketallization well-known to those skilled in the art and well documented e.g. in "Organic Functional Group Preparations", Volume III, pp. 2-53, Academic Press, N.Y. (1972) by Stanley R. Sandler and Wolf Karo.
  • a solution of a cyclohexenone compound (II) in a halogen-hydrocarbon or aromatic hydrocarbon solvent (5 to 10 parts by weight) is mixed with a 3-substituted propyleneglycol (1 to 5 molar equivalents) and an arylsulfonic acid (0.01 to 0.1 molar equivalent), and the mixed solution is refluxed with heating for 5 to 20 hours under azeotropic dehydration.
  • amounts show ratios to cyclohexenone compound (II)).
  • the reaction mixture is made alkaline with aqueous alkali, extracted with a water-immiscible solvent, washed, dried and concentrated to give an objective 1,4-dioxaspiro[4,5]decene compound (I).
  • a solution of a cyclohexenone compound (II) and an epihalohydrin (III in a reactive form) (1 to 2 molar equivalents) in a halogenohydrocarbon solvent (5 to 20 parts by weight) is mixed with a solution of stannic chloride (0.1 to 2 molar equivalents) in the same halogenohydrocarbon solvent (0.1 to 1 part by weight), and the mixture is allowed to stand for 3 hours at room temperature.
  • Amounts show ratios to said cyclohexenone compound (II).
  • the reaction mixture is made alkaline with aqueous alkali to pH 10 and extracted with a water-immiscible solvent. The extract solution is washed, dried and concentrated to give an objective 1,4-dioxaspiro[4,5]decene compound (I).
  • 1,4-Dioxaspiro[4,5]decene compound (I) thus prepared is usually a diastereomer mixture due to two or three asymmetric carbon atoms at the positions 2 and 4 of 1,3-dioxolane ring part and the position linked to X group when saturated.
  • Halogenating reagents used here include molecular halogen, bromine chloride, iodine chloride, quaternary ammonium perhalide, N-haloamide, N-haloimide and other conventional halogenating reagents for this type of reaction.
  • the reaction is, if required, carried out in the presence of acid-acceptor and in a solvent according to a conventional manner to give the halogenated product (Ib).
  • the aromatization is carried out by the action of a base, acid, adsorbing agent, metal salt or heating.
  • Said starting 1,4-dioxaspiro[4,5]decene compound (I) in which the dotted line represents a double bond and X is halogen can be prepared by the method as given in Sections [2] or [3] of this specification above.
  • Said 1,4-dioxaspiro[4,5]decene compound (I) where the dotted line represents two double bonds and X is hydrogen can be made by a known dehydrohalogenation with a base e.g. aliphatic amine or aromatic amine, if required under heating.
  • An inorganic base and a Lewis acid are also used as reagents for this reaction due to dehydrohalogenation and prototropy.
  • the starting 1,4-dioxaspiro[4,5]decene compound (I) is treated with an aliphatic amine e.g. lower alkylamine, di-lower alkylamine, tri-lower alkylamine, lower alkyleneamine, oxa-lower alkyleneamine, di-lower cycloalkylamine, 1,5-diazabicyclo[5,4,0]undecene-5, 1,4-diazabicyclo[2,2,2]octane, quinuclidine, 1,5-diazabicyclo[4,3,0]nonene-5; aromatic base e.g.
  • pyridine picoline or quinoline
  • lower alkanoate aromatic carboxylate, lower alkoxide, phenolate, carbonate salt of alkali metal
  • alkali metal hydroxide or like bases.
  • this reaction requires higher temperature e.g. 40° to 150° C., for several hours to a few days.
  • Most preferable base is a secondary amine having a boiling point between 80° C. to 200° C.
  • the starting 1,4-dioxaspiro[4,5]decene compound (I) is treated with a mineral acid, carboxylic acid, sulfonic acid or Lewis acid.
  • a mineral acid carboxylic acid, sulfonic acid or Lewis acid.
  • instability of the starting ketal compound (I) to a proton acid prefers non-protonic acid i.e. Lewis acid for this step of reaction.
  • a Lewis acid e.g. beryllium chloride, boron trichloride, boron tribromide, magnesium chloride, aluminum chloride, silicon tetrachloride, zirconium tetrachloride, titanium tetrachloride, stannic chloride, antimony trichloride, niobium pentachloride or tellurium tetrachloride; more preferably beryllium chloride, boron trichloride, boron tribromide, aluminium chloride, titanium tetrachloride stannic chloride or other Lewis acid; the reaction proceeds at a very low temperature e.g. -70° to 0° C.
  • a Lewis acid e.g. beryllium chloride, boron trichloride, boron tribromide, magnesium chloride, aluminum chloride, silicon tetrachloride, zirconium tetrachloride, titanium tetrachloride,
  • the reaction condition depends on the selected Lewis acid.
  • a catalytic amount to excess amount of said Lewis acid per selected starting compound (I) e.g. 1 to 6 molar equivalent may be used.
  • Aromatization of this type is suitable for Compounds (I) having alkylamino or alkenyleneamino as Y. This is done in presence of an additional reagent selected from tertiary amines such as tri-lower alkylamine, N-lower alkyl-lower alkyleneamine, N-lower alkyl-oxa-lower alkyleneamine, N-lower aryl-di-lower alkylamine and polycyclic aza-lower hydrocarbon e.g.
  • the amount of the tertiary amine to be added is preferably 1 to 8 molar equivalents per the starting compound (I) for accelerating the reaction and improve the yield.
  • This reaction is carried out at sub-zero to room temperature, preferably at -80° C. to 20° C.
  • the reaction is usually complete within 0.1 to 50 hours.
  • the reaction time varies considerably depending on choosed reaction conditions e.g. solvent, selected sort of Lewis acid and/or the presence or absence and sort of the additional reagent.
  • a solution of 1,4-dioxaspiro[4,5]decene compound (I) and a tri-lower alkylamine (1 to 8 molar equivalents) in a halogenohydrocarbon solvent (10 to 20 parts by weight) cooled at -50° to -10° C. is mixed dropwise with a solution of a stannic halide (1 to 5 molar equivalents) in the same or different halogenohydrocarbon solvent (1 to 10 parts by weight), kept at the same temperature for a few minutes, warmed to room temperature and allowed to stand at the same temperature for 1 to 10 hours.
  • Said aromatization with an adsorbing agent can be carried out with e.g. alumina, silica gel, magnesium silicate, calcium carbonate, zinc oxide, etc.
  • Said aromatization by heating can be carried out and at an elevated temperature sufficient to cause pyrolytic dehydrohalogenation e.g. at around 150° C. preferably in an inert solvent.
  • aromatizations are carried out in an inert solvent e.g. hydrocarbon-(e.g. benzene, toluene, xylene, ligroin), halogenohydrocarbon-(e.g. chlorobenzene, dichloromethane, dichloroethane, trichloroethane, chloroform), ether-(e.g. diethyl ether, dibutyl ether, dioxane), nitrohydrocarbon-(e.g. nitrobenzene, nitromethane), ester-(e.g.
  • hydrocarbon- e.g. benzene, toluene, xylene, ligroin
  • halogenohydrocarbon- e.g. chlorobenzene, dichloromethane, dichloroethane, trichloroethane, chloroform
  • reagent When selected reagent is a liquid, it may also serve as a solvent.
  • aromatization products can be isolated by removing unreacted starting materials, excess reagent, solvent, by-product, etc. from the reaction mixture by a conventional manner (e.g. concentration, washing, adsorption, extraction, precipitation, crystallization) and purifying by a conventional method (e.g. fractional extraction, recrystallization, washing, adsorption, elution, chromatography).
  • a conventional manner e.g. concentration, washing, adsorption, extraction, precipitation, crystallization
  • purifying e.g. fractional extraction, recrystallization, washing, adsorption, elution, chromatography
  • reaction products or crude material can be used as the starting materials for succeeding reactions without isolation or further purification.
  • the product, 3-substituted-2-hydroxypropyl aryl ther (V), is a ⁇ -blocker for treating circulatory diseases, as explained above.
  • the compound (V) can be, if required, deprotected, protected or modified at the P, Q, R or Y group to obtain more pharmacologically preferable substances and serve as intermediates therefor.
  • Y When Y is a basic group, it should be neutrallized beforehand with a suitable acid e.g. p-toluenesulfonic acid.
  • a suitable acid e.g. p-toluenesulfonic acid.
  • the reaction mixture is adjusted to pH 9 with 2.5N aqueous sodium hydroxide with stirring, and the formed toluene layer is separated.
  • the water layer is washed with benzene (200 parts). Toluene layer and benzene washing are combined, washed twice with water (500 parts) and dried over anhydrous sodium sulfate (500 parts). The drying agent is filtered off, and the filtrate is concentrated under reduced pressure.
  • the obtained residue (143 parts) is dissolved in benzene (300 parts), stirred with active charcoal (50 parts) for 30 minutes and filtered through a filter-bed of siliceous earth.
  • a mixture of 3-p-toluenesulfonyloxypropyleneglycol acetonide (2 molar equivalents), 5-bromo-1-p-toluenesulfonyl-4-oxo-4,5,6,7-tetrahydroindole (100 parts), hydrochloric acid (1 molar equivalent) and benzene (500 to 2000 parts) is refluxed for 21 hours under azeotropic dehydration. After cooling, the reaction mixture is adjusted to pH 10 with 5N-sodium hydroxide, shaken and water layer drained. Organic layer is washed with water, (100 parts) and dried over anhydrous sodium sulfate (50 parts). The drying agent is removed by filtration.
  • the filtrate is then concentrated under reduced pressure at a temperature below 50° C. to leave amorphous 4'-p-toluenesulfonyloxy-1-p-toluenesulfonyl-5-bromo-4,5,6,7-tetrahydroindole-4-spiro-2'-[1,3]-dioxolane diastereomer mixture in 42% yield.
  • the product is shown in Table I, Part 6, No. 18.
  • a mixture of 5-bromo-1-p-toluenesulfonyl-4-oxo-4,5,6,7-tetrahydroindole (100 parts), epibromohydrin (1.2 molar equivalents) and stannic chloride (0.1 molar equivalent) in carbon tetrachloride (1500 parts) is kept at 0° C. to 2° C. for 19 hours.
  • the reaction mixture is carefully mixed with 5N-sodium hydroxide to adjust at pH 10, shaken and organic layer separated.
  • Aqueous washings are combined and washed with dichloromethane (50 parts).
  • Dichloromethane solution and dichloromethane washing are combined, washed with water (30 parts), are dried over anhydrous sodium sulfate. After 1 hour, the drying agent is removed by filtration, and obtained filtrate is concentrated to dryness under reduced pressure.
  • Obtained residue (132 parts) is dissolved in dichloromethane (270 parts), allowed to stand for half an hour with active charcoal (30 parts), and filtered through Florisil filter-bed. The resulting filtrate is concentrated under reduced pressure to dryness at below 30° C. and the obtained residue is triturated in a small amount of a mixture of benzene and dichloromethane to give amorphous powder.
  • the same product can be prepared in 70 to 80% yield by heating 4'-bromomethyl-5-bromo-1-p-toluenesulfonyl-4,5,6,7-tetrahydroindole-4-spiro-[1,3]dioxolane or 4'-p-toluenesulfonyloxymethyl-5-bromo-1-p-toluenesulfonyl-4,5,6,7-tetrahydroindole-4-spiro-2'-[1,3]dioxolane in isopropylamine for 18 hours. ##STR69##
  • a mixture of a 2-substituted-1,4-dioxaspiro[4,5]decene (1) (100 parts), a base (6) (1 to 5 molar equivalents) and a solvent (500 to 2000 parts) are heated at 75° to 120° C. for 3 to 50 hours. After cooling, the reaction mixture is diluted with water and ethyl acetate. Formed organic layer is separated and washed with water, dried and concentrated to dryness. The residue is purified to give a 3-substituted-2-hydroxypropyl aryl ether (5).
  • a cyclohexadiene compound (1) is treated with a base under the reaction conditions given in Table VI to afford the corresponding 3-substituted-2-hydroxypropyl aryl ether (5).
  • the crystals are identified as pindolol by comparing with a pindolol sample (m.p. 172.5°-173° C.) by mixed melting point determination and comparison of thin-layer chromatograms, IR-spectra and proton-magnetic resonance spectra.
  • Residue (172 parts) is recrystallized from ethanol-hydrochloric acid giving 6-(3-isopropylamino-2-hydroxypropoxy)benzothiazole) (65 parts) in 57% yield. mp. 132°-134° C. (hydrochloride trihydrate).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Indole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US06/127,521 1979-03-07 1980-03-05 Process for preparing indoles Expired - Lifetime US4506079A (en)

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Application Number Priority Date Filing Date Title
JP54-27010 1979-03-07
JP2701079A JPS55118432A (en) 1979-03-07 1979-03-07 2-spipo-1,3-dioxolane compound and new synthesis of aromatic ether by its ring opening reaction
JP55-10399 1980-01-30
JP1039980A JPS56108764A (en) 1980-01-30 1980-01-30 Novel synthesis of beta-blocker

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CA (1) CA1139760A (enrdf_load_stackoverflow)
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DE (1) DE3008902A1 (enrdf_load_stackoverflow)
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4582905A (en) * 1979-03-07 1986-04-15 Shionogi & Co., Ltd. 1,4-Dioxaspiro(4,5)decene compounds

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US4990668A (en) * 1985-12-04 1991-02-05 E. I. Du Pont De Nemours And Company Optically active aryloxypropanolamines and arylethanolamines
AU2003237705B2 (en) 2002-06-05 2009-07-30 F. Hoffmann-La Roche Ag 1-sulfonyl-4-aminoalkoxy indole derivatives as 5-HT6-receptor modulators for the treatment of CNS-disorders
AU2003289903B2 (en) * 2002-12-03 2008-06-26 F. Hoffmann-La Roche Ag Aminoalkoxyindoles as 5-HT6-receptor ligands for the treatment of CNS-disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3758502A (en) * 1970-09-30 1973-09-11 F Seemann Organic compounds
US3772329A (en) * 1971-01-21 1973-11-13 Polaroid Corp 7-sulfamoyl indole derivatives

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1139760A (en) * 1979-03-07 1983-01-18 Makiko Sakai 1,4-dioxaspiro¬4,5| decene compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3758502A (en) * 1970-09-30 1973-09-11 F Seemann Organic compounds
US3772329A (en) * 1971-01-21 1973-11-13 Polaroid Corp 7-sulfamoyl indole derivatives

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4582905A (en) * 1979-03-07 1986-04-15 Shionogi & Co., Ltd. 1,4-Dioxaspiro(4,5)decene compounds

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IT8067367A0 (it) 1980-03-07
GB2058745B (en) 1983-05-25
DE3008902C2 (enrdf_load_stackoverflow) 1991-05-02
FR2450829A1 (fr) 1980-10-03
GB2058745A (en) 1981-04-15
FR2450829B1 (enrdf_load_stackoverflow) 1982-12-10
US4582905A (en) 1986-04-15
CA1139760A (en) 1983-01-18
IT1129805B (it) 1986-06-11
CH646968A5 (de) 1984-12-28
DE3008902A1 (de) 1980-09-18

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